Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [¹¹C]PBR28 PET

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• 作者：Xia Shao ; Xueding Wang ; Sean J. English ; Timothy Desmond ; Phillip S. Sherman ; Carole A. Quesada ; Mor ; R. Piert
• 关键词：[11C]PBR28 ; TSPO ; Systemic adjuvant arthritis ; Carrageenan-induced inflammation macrophages ; RAW 264.7 cells
• 刊名：Nuclear Medicine and Biology
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：40
• 期：7
• 页码：906-911
• 全文大小：1187 K

文摘

Introduction

[¹¹C] PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models.

Methods

Acute inflammation was induced by local carrageenan injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [¹¹C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak ¹¹C-PBR28 SUV (SUV_peak) and area under the curve (AUC_SUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [¹¹C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures.

Results

LPS-stimulated macrophages displayed dose-dependent increased [¹¹C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUV_peak and AUC_SUV of carrageenan-treated paws was significantly increased compared to controls. Also, the [¹¹C]PBR28 uptake ratio of carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [¹¹C]PBR28 SUV_peak and AUC_SUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips.

Conclusions

Based on our initial data, [¹¹C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.